Vitamin K antagonists (VKAs) prevent stroke in atrial fibrillation (AF) at the cost of bleeding risk. To determine major bleeding rates in AF patients, we conducted a systematic review that identified 51 eligible studies including more than 342,699 patients. The pooled estimate of the rate of major bleeding was 2.51 (99% confidence interval: 2.03-3.11) bleeds per 100 patient-years. The results represent the best estimates of bleeding risk that most patients contemplating VKA use may expect.